Drugs for Headaches 1

Headache Common symptom Triggered by a variety of stimuli Stress, fatigue, acute illness, sensitivity to alcohol Mild episodes Relieved by over-the-counter drugs (OTCs) (e.g., aspirin, acetaminophen) Severe headaches Migraine, cluster, tension-type 2

Medication Overuse Headache 3

Headaches Identifiable underlying causes No identifiable cause Severe hypertension, hyperthyroidism, tumor, infection, and disorders of the eye, nose, sinuses, and throat No identifiable cause Migraine Cluster 4

Headaches Migraine headache I: characteristics and overview of treatment Migraine headache II: abortive therapy Migraine headache III: preventive therapy Cluster headaches Tension-type headache 5

Headaches Overview of treatment Drugs used in two ways Abort an ongoing attack Aspirin-like drugs, opioid analgesics, migraine-specific drugs Prevent attacks from occurring Beta blockers, TCAs, and antiepileptic drugs TCAs = tricyclic antidepressants. 6

Migraine Headache I Characteristics Throbbing head pain of moderate to severe intensity Nausea and vomiting Sensitivity to light and sound Highly debilitating 7

Migraine Headache I Characteristics (cont’d) Hormonal component Family history typical Two primary forms Migraine with aura Preceded by visual symptoms Migraine without aura More common than with aura 8

Migraine Headache I Pathophysiology Neurovascular disorder that involves dilation and inflammation of intracranial blood vessels Vasodilation leads to pain Neurons of the trigeminal vascular system 9

Migraine Headache I Overview of treatment Aborting an ongoing attack Nonspecific analgesics Aspirin-like drugs and opioid analgesics Migraine-specific drugs Ergot alkaloids, serotonin1B/1D receptor agonists (triptans) Preventing attacks from occurring Beta blockers, TCAs, antiepileptic drugs 10

Migraine Headache I Nondrug measures Adequate sleep Exercise Avoiding triggers Once headache begins Dark room with ice pack to neck 11

Migraine Headache II: Abortive Therapy Objective: to eliminate headache pain and suppress associated nausea/vomiting Earliest treatment possible Route of administration Oral not effective owing to GI distress Injection, inhalation, rectal suppository may be more effective Antiemetics 12

Selection of Drugs Mild to moderate headache Moderate to severe Aspirin-like drugs Aspirin, acetaminophen, ibuprofen, and other aspirin-like analgesics Moderate to severe Migraine-specific drug Opioid analgesics Antiemetics 13

Ergot Alkaloids Ergotamine Mechanism of antimigraine action Exact mechanism unknown Therapeutic uses Drug of choice to stop an ongoing migraine Pharmacokinetics PO, sublingual, rectal, or inhalation Adverse effects Nausea/vomiting, weakness in the legs, myalgia, numbness and tingling in fingers or toes, angina-like pain, tachycardia or bradycardia 14

Ergot Alkaloids Ergotamine (cont’d) Overdose Drug interactions Ergotism Drug interactions Triptans, CYP3A4 inhibitors Physical dependence Risk of regular daily use Contraindications Hepatic or renal impairment 15

Ergot Alkaloids Dihydroergotamine Therapeutic uses Drug of choice for terminating migraine and cluster headaches Pharmacologic effects Similar to ergotamine Pharmacokinetics Only parenteral or nasal spray administration—not oral 16

Ergot Alkaloids Dihydroergotamine (cont’d) Drug interactions CYP3A4 inhibitors, serotonin agonist Contraindications Patients with coronary artery disease (CAD), peripheral vascular disease (PVD), sepsis, pregnancy, hepatic or renal impairment 17

Serotonin1B/1D Receptor Agonists Sumatriptan (Imitrex) Mechanism of action Binds to receptors on intracranial blood vessels and causes vasoconstriction Diminishes perivascular inflammation Therapeutic use Aborting an ongoing migraine attack to relieve headache and associated symptoms Pharmacokinetics Oral or intranasal administration 18

Serotonin1B/1D Receptor Agonists Sumatriptan (cont’d) Adverse effects Chest symptoms Transient “heavy arms” or “chest pressure” experienced by 50% of users Coronary vasospasm Rare angina secondary to vasospasm Teratogenesis Others Vertigo, malaise, fatigue, tingling sensations Very bad taste when taken in intranasal form 19

Serotonin1B/1D Receptor Agonists Drug interactions Ergot alkaloids, sumatriptan, other triptans (all cause vasoconstriction) Preparations, dosage, and administration Oral Nasal spray 20

Serotonin1B/1D Receptor Agonists Other serotonin1B/1D receptor agonists Zolmitriptan Naratriptan Rizatriptan Almotriptan Frovatriptan Eletriptan 21

Migraine Headache III Beta blockers Tricyclic antidepressants Preferred drugs for migraine prevention Tricyclic antidepressants Antiepileptic drugs Divalproex Topiramate Estrogens (for menstrual migraine) 22

Migraine Headache III Other drugs for prophylaxis Calcium channel blockers Candesartan, an angiotensin II receptor blocker (ARB) Supplements Riboflavin Coenzyme Q-10 Feverfew Butterbur 23

Cluster Headaches Characteristics Occur in a series or “cluster” of attacks Each attack lasts 15 minutes to 2 hours Severe, throbbing, unilateral pain near the eye Lacrimation, conjunctival redness, nasal congestion, rhinorrhea, ptosis, miosis on the same side of the headache 1–2 attacks every day for 2–3 months An attack-free interval of months to years separates clusters 24

Cluster Headaches Treatment Primary therapy directed at prophylaxis 25

Tension-Type Headache Characteristics Most common form of headache Moderate, nonthrobbing pain Usually located in a “head band” distribution May be episodic or chronic Treatment Nonopioid analgesics Patient teaching on how to manage stress 26